Recent findings indicate that exogenous gangliosides (membrane glycolipids) enhance: 1) neuritic outgrowth in vitro; 2) lesion-induced axonal growth ("sprouting") in vivo; and 3) recovery of function. The purpose of the study is to provide preliminary information concerning the degree to which ganglioside treatments promote the formation of synaptic connections ("synaptogenesis") after lesions. The hypothesis is that ganglioside treatments result in enhancements of postlesion synaptogenesis which correlate with the enhancements in neuritogenesis in vitro and recovery of function in vivo. Using the denervated hippocampus as a model structure, the specific aims are to evaluate the degree to which monosialoganglioside (GM1) treatments: 1) promote lesion-induced synaptogenesis; 2) accelerate the onset or increase the magnitude of the sprouting response; and 3) alter the time course of decreases in the numbers of degenerating terminals and synapses. The experimental approach will be to perform quantitative electron microscopic analyses. The number of identifiable axon terminals, synapses, postsynaptic specializations, and degenerating elements will be counted in the denervated zone of the dentate gyrus at 4, 10, and 30 days after unilateral lesions of the entorhinal cortex in GM1- and control-treated adult rats. The results will be correlated with recently published findings that exogenous gangliosides: 1) promote neuritogenesis in vitro; and 2) enhance behavioral recovery after entorhinal lesions in vivo. The proposed research will generate new and useful information about the utility of GM1 treatments for promoting synaptogenesis after brain damage. We expect to obtain data which will guide future studies concerning cellular mechanisms of gangliosides' effects on sprouting (in vivo and in vitro) and the functional significance of these effects.